Biomarkers associated with immune-related adverse events induced by immune checkpoint inhibitors

Table 1 Blood cell biomarkers of immune-related adverse events

Biomarker	ICI type	Patients	Study cohort	irAE type	Judgment	Ref.
CD4+ T cell	CTLA-4, PD-1	17	8/17 (47%) irAEs, among them, 4 multiple irAEs	NA	CD4+ T cells increased during irAEs	[34]
CD8+ T cell	CTLA-4, PD-1	17	8/17 (47%) irAEs, among them, 4 multiple irAEs	NA	CD8+ T cells increased during irAEs	[34]
B cell	CTLA-4, PD-1	23	13/23 (57%) irAEs	NA	Low levels of CD21lo B cells at baseline in the irAE group, and significantly increase after the first cycle of combined CTLA-4 and PD-1 inhibitor treatment	[35]
White blood cell count and relative lymphocyte count	PD-1	101	38/101 (38%) irAEs. Among them, 6 multiple irAEs, 2 combined irAEs, 4 continuous irAEs	NA	An increase in white blood cell and a decrease in relative lymphocyte count were associated with the occurrence of G3/4 irAEs	[36]
Absolute eosinophil count	PD-1	321	18% ICI pneumonia in patients with an average age of 62.7 years	Lung irAEs	The absolute eosinophil count of patients with ICI-pneumonia was significantly higher than that of no ICI-pneumonia patients	[37]
Absolute lymphocyte count	PD-1	171	73/171 (42.7%) irAEs	NA	At 2 wk after initiation of treatment, an increase in absolute lymphocyte count was significantly associated with an increased risk of irAEs	[38]
Neutrophil/lymphocyte ratio	PD-1	275	121/275 (44.0%) irAEs, 86 with one irAEs, 26 with two irAEs, 9 with three or more irAEs, Severe irAEs (> grade 3) occurred in 29 (10.5%)	Lung irAEs	Increased neutrophil/lymphocyte ratio can predict the severity of subsequent irAEs pneumonia with high accuracy, and the higher the NLR value, the more severe irAEs occurs	[39]
	PD-1	92	45/92 (48.9%) irAEs	NA	Before treatment, neutrophil/lymphocyte ratio > 2.3 was significantly associated with an increased risk of irAEs	[40]
Lymphocyte/monocyte ratio	PD-1	92	45/92 (48.9%) irAEs	NA	Before treatment, lymphocyte/monocyte ratio > 1.6 significantly reduced the risk of irAEs	[40]
Absolute monocyte count	CTLA-4, PD-1, PD-L1	470	33% irAEs	NA	The incidence of irAEs was significantly associated with higher baseline absolute monocyte count	[41]
Platelet count	CTLA-4, PD-1, PD-L1	470	33% irAEs	NA	The incidence of irAEs was significantly associated with higher baseline platelet count	[41]
Platelet/lymphocyte ratio	CTLA-4, PD-1, PD-L1	470	33% irAEs	NA	The incidence of IrAEs was significantly associated with lower baseline platelet/lymphocyte ratio	[42]

irAEs: Immune-related adverse events; ICI: Immune checkpoint inhibitors.